Thiadiazole



Unite ttes 3,99%,721 TIEADEAZGLE Jan Hendrik Uhienbroek and Johan Dirk Biiloo, Van Houtenlaan, Wcesp, Netherlands, assignors to North American Philips Qompany, Inc, New York, N.Y., a corporation of Delaware No Drawing. Filed Feb. 13, 1959, Ser. No. 792,953 Claims priority, application Netherlands Feb. 13, 1958 29 Claims. (Cl. 167-33) It is known that 1.2.4-thiadiazoles, in which both carbon atoms of the ring carry monovalent organic radicals linked through sulphur, might be used for combating noxious insects and larvae of them. These organic radicals may be alkyl-, cycloalkyl-, aralkyl-, alkoxyalkyl-, aryloxyalkyl-, carbethoxyalkylor hydroxyalkyl groups.

It has now been found that 1.2.4-thiadiazoles, in which a. halogen atom is linked to one of the carbon atoms of the ring are active against noxious organisms and in particular have a nematocide effect.

The present invention relates to a method of producing a means for combating noxious organisms and in particular nematodes, characterized in that a compound of the general formula:

in which Hlg represents a halogen atom and R represents a phenyl group or a group R .S-, in which R represents a whether or not substituted, saturated or unsaturated, alkyl-, cycloalkyl-, arylor aralkyl group, the aliphatic chain whether or not being interrupted by oxygen or sulphur, is mixed with inert, solid or fluid carriers, if desired with the addition of surface-active materials and/ or dispersion agents.

A satisfactory nematocide effect have, in particular, the compounds according .to the invention, in which I-Ilg represents a chlorine atom and R represents an alkyl group with 1 to 12 carbon atoms such as methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl-, isoamyl-, hexylor octyl group or an oxygen interrupted alkyl group such as an ethoxyethyl group or an unsaturated group, for example an allyl group and further compounds, in which R represents a phenyl-, 4-chlorophenyl-, 4-methylphenyl group or a benzylor 4-chlorobenzyl group or a phenoxyethyl group.

Excellent nematocides are compounds according to the invention in which Hlg is a chlorine atom and R represents a phenyl group, as well as those in which R represents an unbranched alkyl. group comprising 1 to 6 carbon atoms, an allyl group, an ethoxyethyl group or a phenyl-, 4-chlorophenyl or 4-methylphenyl group or a benzylor 4-chlorobenzyl group.

Particularly those nematodes are attacked by compounds according to the invention which cause eel worm diseases in plants, for example Heterodera species, for example larvae of Heterodera rostochz'ensis (potato cysticolous eel worm), Meloidogyne species (root knob eel worms) Ditylenchus species (stem eel worms), Pratylenchus species, Hoplolaimus species and larvae of Anguina triiicz (wheat gall eel worms).

Tests showing the nematocide etfect of compounds according to the invention were carried out as follows.

30 mgs. of the compound to be tested were finely ground with the addition of 5 drops of a solution of 5% of polyethylenemonolaurate and subsequently suspended in 30 ccs. of water. By diluting this suspension with water suspensions of different concentrations were obtained which were used for carrying out the tests.

1.5 ccs. of the suspension to be tested and subsequently approximately 100 nematodes were introduced into an embryo tray of 4 by 4 cm. having a cavity of 3.5 ccs. Subsequently, the tray was closed by means of a roughly ground glass guard in such manner as to admit a quantity of oxygen sufiicient to prevent immobilisation of the nematodes by lack of oxygen. By means of a binocular the vitality of the nematodes was determined after 4, 24, 48 and 140 hours respectively.

In this manner the lowestconcentration of active compound in the suspension used was determined, which resulted in 100% kill of the test specimen after 140 hours exposure.

The tests were carried out on larvae of Heterodera rostochiensis lured for two days from their cysts, Ditylenchus dipsaci and larvae of Anguina tritici (both specimens soaked for 17 hours from 'dry condition).

The results of these tests are listed in Table I, which states the minimum lethal dosage of the investigated compound, killing all the test specimens within 140 hours exposure. The minimum lethal dosage stated is the concentration of the active compound of the suspension used, expressed in parts by weight of active compound per million parts by weight of diluent (water).

TABLE I Compound Nematodes i i N O-Ol Heterodera Ditylenchus Ang'uz'na S rostochiensis dipsaci tritici 12 25 50 6 100 25 6 50 12 6 50 25 50 500 100 6 25 12 12 100 50 CH3.OH2.CH(CH3).S. 50 1,000 100 I1.C5H11.S 6 50 6 CH3.CH(CH:).CH2.CH2.S 6 100 12 n. O 61113.8 6 25 6 50 250 50 100 1,000 1, 000 4 50 15 3 100 25 12 500 25 12 1,000 25 12 1, 000 12 12 50 12 6 1, 000 6 4-N 0 1. 06115. CH2.S 1, 000 1, 000 50 Table II states the results of a series of tests with 3- n.butylmercapto-S-chloro-l.2.4-thiadiazole in vitro, carried out as before. The table states the percentage of nematodes killed within 140 hours exposition under the influence of the thiadiazole referred to.

TABLE II Concentration of active substance in parts per million Nematode Heterodera rostuchiensz's (larvae) 100 100 100 100 100 100 Ditylenchus dipsaci 100 100 30 Anguinctritici (larvae) 100 100 100 100 60 and subsequently stored for 24 days in cups at approximately 15 C. In order to prevent drying out of the soil the cups were covered with a polythene foil. The nematodes were subsequentl-ywashed out of the soil in the manner referred to by 'I. W. Seinhorst and the survivors were counted (see Nematologica, vol. 1, pages 249 to 267 (1956)). The same was done with blank-tests without adding active substance to the soil.

The tests were carried out five times.

Table III states the average result of these tests for each of the following compounds:

UE 9:3-phenyl-5-chloro-1.2.4-thiadiazole, I UE 18=B-methylmercapto-S-chloro-1.2.4-thiadiazole, UE 19':3-n.butylmercapto-5-chloro-1.2.4-thiadiazole, UE 32:3-n.propylrnercapto-5-chloro-1.2.4-thiadiazole.

TABLE n1 Mg. active Surviving Kill Compound substance per hematodes percentage 250 g. of soil UE 1s; so 24 96 25 55 90 10 40 93 0 534 Principally known methods maybe used for producing the pesticidal preparations. Thus, for example, the active compounds according to the invention may be mixed with a pulverulent inert carrier, for'exa-mple chalk, dolomite, attapulgite, kaolin or pipe clay, or dissolved or dispersed in an inert solvent such as toluene, xylene, aliphatic or aromatic ketones, for example acetone, methyl-ethylketone or cyclohexanone, or mixtures of them with said hydrocarbons, if desired with the addition of surface-active materials and/or dispersion agentsj As an alternative, these preparations may be mixed with synthetic tertilisers.

For example, a dust is prepared by grinding approximately 5 parts by weight of an active compound according to the invention together with approximately 95 parts by weight of kieselguhr to an average particle size of approximately ;r.

For example a wettable powder is produced by mixing approximately 50 parts by weight of an active compound according to the invention with approximately 5 parts by weight of oleylamido-methyltaurate, approximately 10 parts by weight of calciumligninsulfonate and approximately 35 parts by weight of dolomite (calcium-magnesium carbonate), this mixture being ground to an average particle size of approximately 10;!

Miscible oils may, for example, be produced by dissolving approximately 25 parts by weight of an active compound according to the invention in a mixture of approximately 10 parts by weight of an active compound according to the invention in a mixture of approximately 10 parts by weight of polyoxyethylenesorbitan fatty acid ester, approximately 10 parts by weight of methylethylketone and approximately 55 parts by weight of xylene.

The compounds according to the invention permit in general,.miscible oils of :high concentration to be produced. Thus, for example, 3-n.butylmercapto-S-chloro- 1.2.4-thiadiazole with xylene can be worked up to a miscible oil containing 80 percent by weight of active material. This may be of importance in practice.

The production of a number of the compounds according the invention has already been described. (See I.

Goerdeler et al., Chem. Berichte 90, 182 et seq. and 892 et seq. (1957).) An amidin salt of isothiouroni-um salt in water in reacted with an equivalent quantity of perchloromethylmercaptan with the addition of soda lye.

Several of the compounds according to the invention, in which R represents the group R 8 have, however, not yet been mentioned in the literature. These compounds can be produced by the aforesaid method from isothiouronium salts and perchloromethylmercaptan. Novel compounds are inter alia those in which in the aforesaid formula R represents one of the following groups: isopropyl, l-methylpropyl, 3-methylpropyl, namyl, n.hexyl, noctyl, n.dodecyl, allyl, ethoxyethyl, phenyl, '4-chl0rophenyl, 4-methylphenyl and phenoxyethyl.

The production of a number of these novel compounds will be described in Examples I to V.

Example I II-PHENYLMERCAPTQ-5(THLORO-l.2A FHIADIAZOLE NE I l l O-Cl In a 3 litre flask, 188.5 gms. (1.0 mole) of phenylisothiouroniumchloride were mixed with 186 gms. (1.0 mole) of perchloromethylmercaptan, 180 ccs. of water and 300 ccs. of methylenechloride, while cooling the flask with ice-water. Subsequently, a solution of 160Jgms. (4.0 mole) of sodium-hydroxide in 500 ccs. of water was slowly added to the mixture, while'stirring vigorously. The rate of adding the soda lye Was such that the temperature did not exceed 5 C. and the mixture did not produce an alkaline reaction. After adding the whole quantity, stirring was continued for half an hour. Subsequently 25 ccs. of ammonia (25% by weight) were added and further stirred for 15 minutes, followed by neutralisation with hydrochloric acid. a

The layer of methylene chloride, in which the reaction product is dissolved, was separated, washed with 0.5 l. of water and dried on anhydrous sodium sulphate. After distilling off the methylene chloride the residue, that is the crude reaction product, was crystallised from petroleum ether (boiling range 40 C. to 60 C.). Yield 148 gms. of 3-phenylmercapto-5-chloro-1.2.4-thiadiazole (yield 65%). Melting point 58 C.

The compounds used in the Examples II to V were produced quite similarly.

Example II 3-n.OCTYLMERCAPTO-fi-CHLORO-l.2A-THIADLAZOLE' 22.4 gms. (yield 68%) of 3-n.octyl-mercapto-S-chloro- 1.2.4-thiadiazole were obtained from 33.6 gms. (0.125 mole) of n.-octylisothiouronium bromide and 23.3 gms. (0.125 mole) of perchloromethylmercaptan. Boiling point: 145 to 146 C. at 8 mms. mercury pressure.

Example III 3-ALLYLMERCAPTO-5-CHLORO-1.ZA-THIADIAZOLE 22.2 gms. (yield 46%) of 3-allylmercapto-5-chloro- 1.2.4-thiadiazole were produced from 49.3 gms. (0.25 mole) of allylisothiouronium bromide and 46.5 gms. (0.25 mole) of perchloromethylmercaptan. Boiling point 117 C. at 15 mms. mercury pressure,

Example IV v 3-(4=-CHLOROBENZYL)MERCAPTO5-CHLORO-1.2.4- THIADIAZOLE 17 gms. (yield 46%) of 3-(4-chlorobenzyl)mercapto- 5-chloro-1.2.4-thiadiazole were produced from 32 gms. (0.13 mole) of 4-chlorobenzylisothiouronium chloride and 25' gms. (0.13 mole) of perchloromethylmercaptan.

diazoles according to the invention.

TABLE IV R2-SC-N II II Melting Boiling point 0. at mm. Yield, N CCl mercury pressure percent point,

110 to 112 at 14 mm 126 to 128 at 14 mm 122 to 124 at 14 mm... 102 to 104 at 0.7 mm. 110 to 112 at 0.02 mru 145 to 146 at 0.8 mm 180 to 183 at 0.05 mm en 65 chlorophenyl 25 4-methylphenyl 51 Phenoxyethyi 40 4-chlor0benzyl 46 a-uitroheuzyl 59 It was moreover found that the compounds according to the invention can be produced from the corresponding 5-amino-l.2.4-thiadiazoles according to the reaction of Sandmeyer, in which the amino compounds are converted into diazonium compounds by means of nitrite, for example sodium nitrite, which diazoniurn compounds are converted into S-chloro-1.2.4-thiadiazoles in the presence of copper powder and a chloride, or in the presence of, for example, cuprous chloride.

This method will be set out in the following examples.

Example VI 3-BENZYLMERCAPTO-5CHLORO-1.2.4-THIADIAZOLE 9.5 gms. (0.043 mole) of 3-benzyhnercapto-5-amino- 1.2.4-thiadiazole were dissolved in 100 ccs. of acetic acid. Whilst cooling with ice a solution of 4.9 gms. (0.07 mole) of sodium nitrite in 50 ccs. of concentrated hydrochloric acid was added dropwise such that the temperature of the mixture did not exceed 20 C. After standing 15 mintries at room temperature, the reaction mixture was poured out while stirring, in a solution of 6 gms. of cuprous chloride in 100 ccs. of concentrated hydrochloric acid. After standing overnight, the mixture obtained was shaken with benzene at room temperature. After concentration by evaporation, the benzenic solution yielded 5.9 gms. (60%) of crude 3-benzylrnercapto-5- chloro-1.2.4-thiadiazole from which the pure compound was obtained by crystallization from methanol. Melting point 49 C.

EXAMPLE VII 3-PHENYL5CHLORO-1.2.4THIADIAZOLE This compound was produced in a manner similar to that used in Example V1.

10.6 gms. (0.06 mole) of 3-phenyl-5-amino-1.2.4-thiadiazole were dissolved in 130 ccs. of acetic acid, followed by adding, while stirring, a solution of 4.56 grns. (0.066 mole) of sodium nitrite in 45 ccs. of concentrated sulphuric acid. The temperature was kept between 5 C. and 10 C. Subsequently, the temperature of the mixture was raised to 18 C. and the mixture was poured out in a solution of 12 gms. (0.120 mole) of cuprous chloride in 120 ccs. of concentrated hydrochloric acid. The 3-phenyl-5chloro-1.2.4-thiadiazole was extracted with petroleum ether (boiling range 40 C. to 60 C.) from the reaction mixture. Yield 6.85 gms. (58%). Melting point 42 C. to 50 C.

What is claimed is:

1. A composition for the control of nematode comprising as an active ingredient a thiadiazole compound corresponding to the general formula:

wherein Hal represents a halogen atom and R represents a radical selected from the group consisting of phenyl and the radical R 8 wherein R represents a radical se- 'lected from the group consisting of alkyl, alkoxyalkyl, allyl, phenyl, methylphenyl, chlorophenyl, benzyl, chlorobenzyl and phenoxyethyl in a nematocidal effective amount, a surface active material and a nematocide adjuvant as a carrier therefor.

2. The composition of claim 1 wherein Hal represents a chlorine atom.

3. The composition of claim 1 wherein R represents an alkyl radical containing 1 to 12 carbon atoms.

4. The composition of claim 1 wherein R represents the ethoxyethyl radical.

5. The composition of claim 1 wherein R represents an nnbranched alkyl radical containing from 1 to 6 carbon atoms.

6. A dust for combating nematodes comprising an intimate mixture of about 5 parts by weight of the active compound of claim 1 and about parts by weight of kieselguhr, said dust having an average particle size of approximately 10;!

7. A wettable powder for combating nematodes comprising an intimate mixture of about 50 parts by weight of the active compound of claim 1, about 5 parts by weight of oleylamidomethyllaurate, about 10 parts by Weight of calcium ligninsulfonate and about 35 parts by weight of dolomite, said powder having an average particle size of about 10a.

8. A miscible oil for combating nematodes comprising a solution of about 25 parts by weight of the active compound of claim 1 in a mixture of about 55 parts by weight of xylene, of about 10 parts by weight of methylethyl-ketone and of about 10 parts by weight of polyoxyethylene-sorbitan fatty acid ester.

9. A composition for the control of nematodes comprising as an active ingredient 3-phenyl-5-chloro-l,2,4- thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

10. A composition for the control of nematodes comprising as an active ingredient 3-alkylmercapto-5-chloro- 1,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

11. A composition for the control of nematodes comprising as an active ingredient 3-ethoxyethylrnercapto-5- chloro-l,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

12. A composition for the control of nematodes comprising as an active ingredient 3-phenylmercapto-5-chloro- 1,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

13. A composition for the control of nematodes comprising as an active ingredient 3-n-butylmercapto-5-chloro-l,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

14. A composition for the control of nematodes comprising as an active ingredient 3-methylmercapto-5-chlor-.1,2,4-thiadiazole in a nematocidal efiective amount, a surface active material and a nematocide adjuvant therefor.

15. A composition for the control of nematodes comprising as an active ingredient 3-(4 -ch1orophenyl)-mercapto-S-chloro-1,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

16. A composition for the control of nematodes comprising as an active ingredient 3-(4 -methylpheny-D-mercapto-S-chloro-l,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

17. A composition for the control of nematodes comprising as an active ingredient S-benzylmercapto-5-chloro- 1,2,4-thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant there for.

18. Acomposi-tion for the control of nematodes comprising-as an active ingredient 3-(4 -henzylmercapto)-5- chloro-1,2,4thiadiazole in a nematocidal effective amount, a surface active material and a nematocide adjuvant therefor.

19. A method of combating nematodes comprising treating the habitat thereof with the composition of claim 1.

20.- A method of combating nematodes comprising treating the habitat thereof with the composition of claim 9. V a

21.A- method of combating nematodes comprising treating the habitat thereof with the composition of claim 10.

22. A method of combating nematodes comprising treating the habitat thereof with the composition of claim 11.

CAD

23.- A method of combating nematodes comprising treating the habitat thereof with the composition of claim 12.

24. A method of combating nematodes comprising treating the habitat thereof with the composition of claim 13.

25. A method of combating nematodes comprising treating the habitat thereof With; the composition of claim 14. V V

26. A method of combating nematodes comprising treating the habitat thereof with the composition of claim 15.

27. A method of combating nematodes comprising treating the habitat thereof with the composition of claim 16.

28. A method of combating nematodes comprising treating the habitat thereof with the composition of claim 17.

29. A method of combating nematodes comprising treating the habitat thereof with the composition of claim 18.

References Cited in the file of this patent UNITED STATES PATENTS 2,285,410 Bousquet et a1. June 9, 1942 2,592,195 Schwarz V. Apr. 8, 1952 2,702,803 Ainsworth 2. Feb. 22, 1955. 2,744,908 Young May 8, 1956 2,863,804 Benghiate et a1. Dec. 9, 1958 OTHER REFERENCES Agr. and Food Chem., vol. 5, pages 159-160, March 

1. A COMPOSITION FOR THE CONTROL OF NEMATODE COMPRISING AS AN ACTIVE INGREDIENT A THIADIAZOLE COMPOUND CORRESPONDING TO THE GENERAL FORMULA: 